Detailed instructions for use of obeticholic acid

1. Introduction to drugs

Obeticholic acid (Obeticholic acid) is a treatment for adults with primary biliary cholangitis (PBC). It can effectively regulate bile acid metabolism and reduce liver inflammation and fibrosis.

2. Applicable groups and diseases

Obeticholic acid is indicated for the treatment of adult patients with primary biliary cholangitis, including patients without cirrhosis and patients with compensated cirrhosis without evidence of significant portal hypertension. It can be used in combination with ursodeoxycholic acid (UDCA) as a complementary treatment when there is an insufficient response to UDCA, or as a monotherapy in patients who cannot tolerate UDCA. However, please note that the indication for this drug was accelerated approval based on reduction of alkaline phosphatase (ALP), and improvement in survival rate or disease-related symptoms has yet to be further confirmed.

3. Possible side effects

The use of obeticholic acid may produce a series of side effects, the more common of which include itching, fatigue, abdominal pain and discomfort, rash, joint pain, sore throat, dizziness, constipation, peripheral edema, palpitations, fever, and thyroid dysfunction. In particular, itching and fatigue are the most common side effects, and itching may sometimes lead to discontinuation of treatment. In addition, post-marketing surveillance also found some serious side effects of hepatobiliary diseases, such as liver failure, new-onset cirrhosis, and elevated bilirubin.

4. Taking method and dosage adjustment

Obeeticholic acid is available as an oral tablet. For patients without evidence of portal hypertension who have an inadequate response to an appropriate dose of UDCA or who are intolerant to UDCA, an initial dose of 5 mg daily for 3 months is recommended. If alkaline phosphatase (ALP) and/or total bilirubin do not decrease sufficiently during this period and the patient tolerates obeticholic acid, the dose may be increased to a maximum dose of 10 mg daily. Patients can take this drug with or without food; however, if bile acid-binding resin is taken at the same time, the interval between taking the two must be at least 4 hours.

5. Drug storage recommendations

Obeeticholic acid tablets should be stored20°C to 25°C, with slight temperature fluctuations allowed (15°C to 30°C). Please keep the medicine out of the reach of children and in its original packaging to prevent deliquescence and deterioration.

6. Mechanism of action

Obeeticholic acid works by activating the farnesoidX receptor (FXR), a nuclear receptor expressed in the liver and intestines. Activation of FXR modulates bile acid, inflammatory, fibrotic, and metabolic pathways, thereby reducing intrahepatocyte bile acid concentrations and reducing hepatic exposure to bile acids. This helps reduce the burden on the liver and promotes bile secretion.

7. Risk of overdose

Clinical trials have shown that overdose of obeticholic acid (2.5 times to 5 times more than the recommended dose) may lead to an increased incidence of adverse liver reactions, including abnormal liver biochemical indicators, ascites, jaundice, and portal hypertension. Therefore, it is necessary to strictly abide by the doctor's instructions during medication to avoid overdose. In the event of overdose, seek medical attention immediately and closely observe changes in the patient's condition.

8. Taboo groups

Obeticholic acid is contraindicated in the following categories of patients: patients with decompensated cirrhosis (e.g.Child-Pugh class B or C), patients with a previous history of decompensation events, patients with compensated cirrhosis with evidence of portal hypertension (e.g. ascites, gastroesophageal varices, sustained thrombocytopenia), and patients with complete biliary obstruction. These patients may be at increased risk with obeticholic acid and should choose other appropriate treatment options.